3-氨基-2-羟基庚酸 | 561066-93-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 3-氨基-2-羟基庚酸
• 英文名称: 3-amino-2-hydroxyheptanoic acid
• CAS: 561066-93-1
• 化学式: C₇H₁₅NO₃
• mdl: MFCD18973133
• 分子量: 161.201
• InChiKey: OLXJKXTUQZYCKF-UHFFFAOYSA-N

物化性质

• 沸点：
  345.1±27.0 °C(Predicted)
• 密度：
  1.146±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.2
• 重原子数：
  11
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.857
• 拓扑面积：
  83.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-氨基-2-羟基庚酸 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.5h， 生成 [1-(Carbamoyl-hydroxy-methyl)-pentyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Benzoylalanine-Derived Ketoamides Carrying Vinylbenzyl Amino Residues:  Discovery of Potent Water-Soluble Calpain Inhibitors with Oral Bioavailability

  摘要：

  Novel benzoylalanine-derived ketoamides were prepared and evaluated for calpain I inhibition. Derivatives carrying vinylbenzyl amino residues in the P-2-P-3 region inhibited calpain in nanomolar concentrations and thus represent a novel class of nonpeptidic calpain inhibitors. Selected examples exhibited an improved pharmacokinetic profile including improved water-solubility and metabolic stability. In particular, these calpain inhibitors showed oral bioavailability in rats as demonstrated by N-(1-benzyl-2-carbamoyl-2-oxoethyl)-2-[E-2-(4-diethylaminomethylphenyl)ethen-1-yl]benzamide (5d). The closely related derivative N-(1-carbamoyl-1-oxohex-1-yl)-2-[E-2-(4-dimethylaminomethylphenyl)-ethen-1-yl]benzamide (5b) was evaluated for neuroprotective efficacy after experimental traumatic brain injury in a fluid percussion model in rats. When administered after injury, 5b reduced the number of damaged neurons by 41%, and this result would be in line with the suggested neuroprotective efficacy of calpain inhibition.

  DOI：

  10.1021/jm0210717
• 作为产物：
  描述：

  1-硝基戊烷 在 palladium on activated charcoal 氢气 、 溶剂黄146 、 三乙胺 作用下， 以 甲醇 、 水 为溶剂， 20.0 ℃ 、413.68 kPa 条件下， 生成 3-氨基-2-羟基庚酸
  参考文献：
  名称：

  Discovery of SCH446211 (SCH6):  A New Ketoamide Inhibitor of the HCV NS3 Serine Protease and HCV Subgenomic RNA Replication

  摘要：

  Introduction of various modified prolines at P-2 and optimization of the P-1 side chain led to the discovery of SCH6 (24, Table 2), a potent ketoamide inhibitor of the HCV NS3 serine protease. In addition to excellent enzyme potency (K-i* = 3.8 nM), 24 was also found to be a potent inhibitor of HCV subgenomic RNA replication with IC50 and IC90 of 40 and 100 nM, respectively. Recently, antiviral activity of 24 was demonstrated with inhibition of the full-length genotype 2a HCV genome. In addition, 24 was found to restore the responsiveness of the interferon regulatory factor 3 (IRF-3) in cells containing HCV RNA replicons.

  DOI：

  10.1021/jm060077j

文献信息

• [EN] CYCLOBUTENEDIONE GROUPS-CONTAINING COMPOUNDS AS INHIBITORS OF HEPATITIS C VIRUS NS3 SERINE PROTEASE<br/>[FR] GROUPES CYCLOBUTENEDIONE CONTENANT DES COMPOSES SERVANT D'INHIBITEURS A LA SERINE PROTEASE NS3 DU VIRUS DE L'HEPATITE C
  申请人：SCHERING CORP

  公开号：WO2005085197A1

  公开（公告）日：2005-09-15

  The present invention discloses novel compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease.

  本发明公开了具有HCV蛋白酶抑制活性的新化合物，以及制备这种化合物的方法。在另一实施方式中，本发明公开了包含这种化合物的药物组合物，以及使用它们治疗与HCV蛋白酶相关的疾病的方法。
• Discovery of SCH446211 (SCH6):  A New Ketoamide Inhibitor of the HCV NS3 Serine Protease and HCV Subgenomic RNA Replication
  作者：Stéphane L. Bogen、Ashok Arasappan、Frank Bennett、Kevin Chen、Edwin Jao、Yi-Tsung Liu、Raymond G. Lovey、Srikanth Venkatraman、Weidong Pan、Tajel Parekh、Russel E. Pike、Sumei Ruan、Rong Liu、Bahige Baroudy、Sony Agrawal、Robert Chase、Paul Ingravallo、John Pichardo、Andrew Prongay、Jean-Marc Brisson、Tony Y. Hsieh、Kuo-Chi Cheng、Scott J. Kemp、Odile E. Levy、Marguerita Lim-Wilby、Susan Y. Tamura、Anil K. Saksena、Viyyoor Girijavallabhan、F. George Njoroge

  DOI：10.1021/jm060077j

  日期：2006.5.1

  Introduction of various modified prolines at P-2 and optimization of the P-1 side chain led to the discovery of SCH6 (24, Table 2), a potent ketoamide inhibitor of the HCV NS3 serine protease. In addition to excellent enzyme potency (K-i* = 3.8 nM), 24 was also found to be a potent inhibitor of HCV subgenomic RNA replication with IC50 and IC90 of 40 and 100 nM, respectively. Recently, antiviral activity of 24 was demonstrated with inhibition of the full-length genotype 2a HCV genome. In addition, 24 was found to restore the responsiveness of the interferon regulatory factor 3 (IRF-3) in cells containing HCV RNA replicons.
• Benzoylalanine-Derived Ketoamides Carrying Vinylbenzyl Amino Residues:  Discovery of Potent Water-Soluble Calpain Inhibitors with Oral Bioavailability
  作者：Wilfried Lubisch、Edith Beckenbach、Sabina Bopp、Hans-Peter Hofmann、Arzu Kartal、Claudia Kästel、Tanja Lindner、Marion Metz-Garrecht、Jutta Reeb、Ferdinand Regner、Michael Vierling、Achim Möller

  DOI：10.1021/jm0210717

  日期：2003.6.1

  Novel benzoylalanine-derived ketoamides were prepared and evaluated for calpain I inhibition. Derivatives carrying vinylbenzyl amino residues in the P-2-P-3 region inhibited calpain in nanomolar concentrations and thus represent a novel class of nonpeptidic calpain inhibitors. Selected examples exhibited an improved pharmacokinetic profile including improved water-solubility and metabolic stability. In particular, these calpain inhibitors showed oral bioavailability in rats as demonstrated by N-(1-benzyl-2-carbamoyl-2-oxoethyl)-2-[E-2-(4-diethylaminomethylphenyl)ethen-1-yl]benzamide (5d). The closely related derivative N-(1-carbamoyl-1-oxohex-1-yl)-2-[E-2-(4-dimethylaminomethylphenyl)-ethen-1-yl]benzamide (5b) was evaluated for neuroprotective efficacy after experimental traumatic brain injury in a fluid percussion model in rats. When administered after injury, 5b reduced the number of damaged neurons by 41%, and this result would be in line with the suggested neuroprotective efficacy of calpain inhibition.